ALDH1A3 Is the Key Isoform That Contributes to Aldehyde Dehydrogenase Activity and Affects <i>in Vitro</i> Proliferation in Cardiac Atrial Appendage Progenitor Cells.

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Serval ID
serval:BIB_B7CC9CD29D69
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ALDH1A3 Is the Key Isoform That Contributes to Aldehyde Dehydrogenase Activity and Affects <i>in Vitro</i> Proliferation in Cardiac Atrial Appendage Progenitor Cells.
Journal
Frontiers in cardiovascular medicine
Author(s)
Puttini S., Plaisance I., Barile L., Cervio E., Milano G., Marcato P., Pedrazzini T., Vassalli G.
ISSN
2297-055X (Print)
ISSN-L
2297-055X
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
5
Pages
90
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
High aldehyde dehydrogenase (ALDH <sup>hi</sup> ) activity has been reported in normal and cancer stem cells. We and others have shown previously that human ALDH <sup>hi</sup> cardiac atrial appendage cells are enriched with stem/progenitor cells. The role of ALDH in these cells is poorly understood but it may come down to the specific ALDH isoform(s) expressed. This study aimed to compare ALDH <sup>hi</sup> and ALDH <sup>lo</sup> atrial cells and to identify the isoform(s) that contribute to ALDH activity, and their functional role. <b>Methods and Results:</b> Cells were isolated from atrial appendage specimens from patients with ischemic and/or valvular heart disease undergoing heart surgery. ALDH <sup>hi</sup> activity assessed with the Aldefluor reagent coincided with primitive surface marker expression (CD34 <sup>+</sup> ). Depending on their ALDH activity, RT-PCR analysis of ALDH <sup>hi</sup> and ALDH <sup>lo</sup> cells demonstrated a differential pattern of pluripotency genes (Oct 4, Nanog) and genes for more established cardiac lineages (Nkx2.5, Tbx5, Mef2c, GATA4). ALDH <sup>hi</sup> cells, but not ALDH <sup>lo</sup> cells, formed clones and were culture-expanded. When cultured under cardiac differentiation conditions, ALDH <sup>hi</sup> cells gave rise to a higher number of cardiomyocytes compared with ALDH <sup>lo</sup> cells. Among 19 ALDH isoforms known in human, ALDH1A3 was most highly expressed in ALDH <sup>hi</sup> atrial cells. Knocking down ALDH1A3, but not ALDH1A1, ALDH1A2, ALDH2, ALDH4A1, or ALDH8A1 using siRNA decreased ALDH activity and cell proliferation in ALDH <sup>hi</sup> cells. Conversely, overexpressing ALDH1A3 with a retroviral vector increased proliferation in ALDH <sup>lo</sup> cells. <b>Conclusions:</b> ALDH1A3 is the key isoform responsible for ALDH activity in ALDH <sup>hi</sup> atrial appendage cells, which have a propensity to differentiate into cardiomyocytes. ALDH1A3 affects <i>in vitro</i> proliferation of these cells.
Keywords
ALDH1A3, aldehyde dehydrogenase, cardiac progenitor cell, heart, stem cell
Pubmed
Open Access
Yes
Create date
13/08/2018 14:40
Last modification date
20/08/2019 16:25
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